In recent years, mouse and human induced pluripotent stem cells (iPS cells) have been established one after another. Yamanaka et al. induced iPS cells by introducing the Oct3/4, Sox2, Klf4 and c-Myc genes into mouse fibroblasts, and forcing the cells to express the genes [WO 2007/069666 A1; Takahashi, K. and Yamanaka, S., Cell, 126: 663-676 (2006)]. Thereafter, it was revealed that iPS cells could also be produced with the 3 factors other than the c-Myc gene [Nakagawa, M. et al., Nat. Biotethnol., 26: 101-106 (2008)]. Furthermore, Yamanaka et al. succeeded in establishing iPS cells by introducing the same 4 genes as those used in the mouse into human skin fibroblasts [WO 2007/069666 A1; Takahashi, K. et al., Cell, 131: 861-872 (2007)]. On the other hand, a group of Thomson et al. produced human iPS cells using Nanog and Lin28 in place of Klf4 and c-Myc [WO 2008/118820 A2; Yu, J. et al., Science, 318: 1917-1920 (2007)]. The iPS cells thus obtained can be differentiated into cells of various tissues after being generated using a cell derived from a patient to be treated, and are therefore expected as a graft source free of rejective reactions in the field of regenerative medicine.
However, tumorigenesis has been reported in relation to transplantation of neurons induced to differentiate from an iPS cell to the mouse brain [Miura K. et al., Nat. Biotechnol., 27: 743-745 (2009)], although tumors are not formed in all neurons derived from the iPS cell. It has been suggested that the starting cell for the establishment of the iPS cell may have a major influence, but no method of generating an iPS cell that ensures the absence of tumorigenesis has been established.
Therefore, there is a demand for a method of selecting an iPS cell that is unlikely to form a tumor when transplanted, out of established iPS cells. As stated above, however, testing by transplantation is too painstaking and takes a long time for judgment.